18-12008848-A-G

Position:

• chr18-12008848-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014214.3(IMPA2):​c.231-1035A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,042 control chromosomes in the GnomAD database, including 12,954 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (12954 hom., cov: 32)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

Genes affected

IMPA2 (HGNC:6051): (inositol monophosphatase 2) This locus encodes an inositol monophosphatase. The encoded protein catalyzes the dephosphoylration of inositol monophosphate and plays an important role in phosphatidylinositol signaling. This locus may be associated with susceptibility to bipolar disorder. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA2	NM_014214.3	c.231-1035A>G		intron_variant		ENST00000269159.8	NP_055029.1
IMPA2	XM_011525659.4	c.182+257A>G		intron_variant			XP_011523961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA2	ENST00000269159.8	c.231-1035A>G		intron_variant		1	NM_014214.3	ENSP00000269159.3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56596 AN: 151922 Hom.: 12910 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56686 AN: 152042 Hom.: 12954 Cov.: 32 AF XY: 0.376 AC XY: 27948 AN XY: 74336

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.363

Alfa AF: 0.252 Hom.: 5286

Bravo AF: 0.402

Asia WGS AF: 0.367 AC: 1279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3786285; hg19: chr18-12008847;